Objective To systematically evaluate the efficacy and safety of proximal gastrectomy (PG) versus total gastrectomy (TG) for the treatment of Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG). Methods PubMed, The Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, and VIP databases were searched for literature comparing the efficacy and safety of PG and TG for the treatment of Siewert type Ⅱ/Ⅲ AEG. The search period was from database inception to March 2023. Meta-analysis was performed using Review Manager 5.4 software. Results A total of 23 articles were included, including 16 retrospective cohort studies, 5 prospective cohort studies, and 2 randomized controlled trials. The total sample size was 2 826 patients, with 1 389 patients undergoing PG and 1 437 patients undergoing TG. Meta-analysis results showed that compared with TG, PG had less intraoperative blood loss [MD=−19.85, 95%CI (−37.20, −2.51), P=0.02] and shorter postoperative hospital stay [MD=−1.23, 95%CI (−2.38, −0.08), P=0.04]. TG had a greater number of lymph nodes dissected [MD=−6.20, 95%CI (−7.68, −4.71), P<0.001] and a lower incidence of reflux esophagitis [MD=3.02, 95%CI (1.24, 7.34), P=0.01]. There were no statistically significant differences between the two surgical approaches in terms of operative time, postoperative survival rate (1-year, 3-year, 5-year), and postoperative overall complications (P>0.05). Conclusion PG has advantages in terms of intraoperative blood loss and postoperative hospital stay, while TG has advantages in terms of the number of lymph nodes dissected and the incidence of reflux esophagitis. There is no significant difference in long-term survival between the two surgical approaches.

Objective To explore the anti-depression mechanism of Kai-Xin-San(KXS)via regulation of neurogenesis in hippocampus of depression-like mice.Methods The extracts of KXS were prepared and the anti-depression effects of KXS were evaluated by behavioral tests on chronic unpredictable mild stress(CUMS)induced depression-like mice.Evaluating depression-like behavior in CUMS mice through sucrose preference test,forced swimming test,tail suspension test,and other methods.Neurogenesis in hippocampus were determined by immunofluorescence assay.In addition,effects of KXS on regulating nestin expression and Wnt/b-catenin signaling pathway were explored by western blotting analysis.Amounts of cortisol,corticotropin-releasing factor(CRF),adrenocorticotropic hormone(ACTH),brain-derived neurotrophic factor(BDNF)and nerve growth factor(NGF)were determined by ELISA tests.Mouse primary neural stem cells(NSC)was used to evaluate the effect of KXS on promoting its proliferation by immunofluorescence assay.In addition,effects of KXS on regulating nestin and Wnt/β-catenin signaling pathway were also explored by Western blotting analysis.Results KXS significantly ameliorated the depression-like behaviors in presence of increased sucrose preference rate and decreased immobile time of tail suspension and forced swimming.KXS significantly promoted the neurogenesis in the hippocampus and expressions of nestin,reduced the expressions of cortisol,CRF,ACTH,increased the expressions of BDNF,NGF,and regulated Wnt/β-catenin signaling pathway.KXS also promoted the proliferation of NSCs and expressions of nestin,enhanced the translocation of b-catenin into nucleus,and regulated the expressions of proteins of Wnt/β-catenin signaling pathway.Conclusion KXS promoted neurogenesis in hippocampus and regulated Wnt/β-catenin pathway,which might contribute to its antidepressant effect.

Objective Evaluation of the effect and mechanism research of Qi-Shen-Yi-Zhi formula on improving learning and memory ability in mice injected with Aβ1-42 in hippocampus.Methods Alzheimer's disease model mice were constructed by injecting β amyloid peptide 1-42 into hippocampus and treated with water extracts of Qi-Shen-Yi-Zhi formula.The cognitive abilities of mice were assessed using Morris water maze and Y maze tests,which measure learning and memory capabilities.HE staining was used to observe the damage and TUNEL method was used to determine apoptosis of hippocampus.Detection of the expression of oxidative factors,inflammatory factors,and related antioxidant proteins and apoptotic proteins in the hippocampal tissue of a mouse model of dementia.Results Both high-dose and low-dose groups of Qi-Shen-Yi-Zhi formula significantly improved cognitive dysfunction in mice injected with Aβ1-42 in hippocampus,and attenuated the damage and apoptosis of the hippocampus.It also inhibited oxidative stress and downregulated the expressions of inflammatory factors IL-6,IL-1β and TNF-a,increased the expression of antioxidant proteins Nrf2 and HO-1,and regulated the expressions of apoptotic proteins Caspase-9,Caspase-3,Bax and Bcl-2.Conclusion Qi-Shen-Yi-Zhi formula improves the learning and memory abilities of mice injected with Aβ1-42 in hippocampus,which might be related to the attenuation of oxidative stress and neuronal inflammation of hippocampus.

Objective To study the effective fraction and mechanism of Lycium barbarum leaves on improving learning and memory ability of subacute aging mice induced by D-galactose injection.Methods The model of subacute aging mice was developed by injection of D-galactose subcutaneously,and different extracts of Lycium barbarum leaves were prepared.The effects of the extracts of Lycium barbarum leaves on the learning and memory ability of model mice were evaluated by Y maze experiment and new object recognition experiment.The pathomorphological changes of hippocampus in mice were observed by hematoxylin-eosin and Nissl staining.The levels of brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),glial cell line-derived neurotrophic factor(GDNF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)and interleukin-10(IL-10)in hippocampus of mice were detected by enzyme-linked immunosorbent assay.The activities of superoxide dismutase(SOD)and the contents of glutathione(GSH)and malondialdehyde(MDA)in hippocampus of mice were detected by related assay kits.Detection of apoptosis in the hippocampal region of mouse brain tissue using the TUNEL method.Western blotting analysis was used to detect the expressions of antioxidant proteins Nrf2,HO-1 and apoptotic proteins Caspase-3,Caspase-9 in hippocampus of mice.Results The water extraction part and 80%alcohol precipitation supernatant part of Lycium barbarum leaves significantly improved the learning and memory ability of model mice,improved the pathological damage of hippocampus in mice,increased the number of Nissl bodies in hippocampus of mice,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF.Pro-inflammatory factors TNF-α,IL-1β and IFN-γ expression declines while anti-inflammatory factor IL-10 expression rises.The activity of SOD and the expression of GSH were increased,and the expression of MDA was decreased.Increase the expression of Nrf2 and HO-1 antioxidant proteins;reduce the expression of Caspase-3 and Caspase-9 apoptosis pathway proteins.Inhibition of apoptosis in the hippocampal region of mouse brain tissue using a model.Conclusion The water extracts and 80%alcohol precipitation supernatant extracts of Lycium barbarum leaves are the effective fractions of Lycium barbarum leaves to improve the learning and memory ability of D-galactose-induced subacute aging mice,and its mechanism might be related to the inhibition of neuronal apoptosis caused by oxidative stress and inflammation.

OBJECTIVE To evaluate the effect of Qishen Yizhi formula on improving learning and memory ability in D-galactose subcutaneous injection induced subacute aging mice.METHODS Subacute aging mice model mice were developed by D-galactose subcutaneous injection and then treated with positive drug donepezil(2 mg·kg-1·d-1)and Qishen Yizhi formula water extracts in low(1.33 g·kg-1·d-1)and high dose group(2.67 g·kg-1·d-1).The learning and memory abilities of mice were evaluated using Morris water maze and Y maze tests;HE staining was used to examine hippocampal damage in model mice;TUNEL was used to detect apoptosis of mouse hippocampal tissue;ELISA was used to detect the expression levels of oxidative stress factors and inflammatory fac-tors in the mouse hippocampus tissue;Western blot was used to detect the expression of signaling pathway proteins related to apoptosis,oxidative stress and inflammatory stress in the hippocampus of mice.RESULTS The water extract of Qishen Yizhi formula signifi-cantly shortened the latency and distance of model mice for reaching the platform in the water maze test(P<0.01),and significantly increased the number of crossing the platform(P<0.01);increased the exploration time and number of the Y maze new arm in model mice(P<0.05);inhibited the TUNEL fluorescence expression in the hippocampus of model mice(P<0.01);upregulated the activity of the oxidative stress factor superoxide dismutase(SOD)(P<0.05)and glutathione(GSH)content(P<0.05),and downregulated malondialdehyde(MDA)content(P<0.05);reduced interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF-α)expression levels(P<0.05,P<0.01);decreased the expression of apoptosis signaling pathway proteins Cleaved Caspase-3 and Caspase-3(P<0.05),upregulated the expression of oxidative stress signaling pathway proteins Nrf2 and HO-1(P<0.05),and downregulated the expression of inflammatory stress signaling pathway proteins p-NF-κB and NF-κB(P<0.05).CONCLUSION Qishen Yizhi for-mula can improve the learning and memory ability of subacute aging model mice injected with D-galactose,which may be related to its inhibitory effect on hippocampal oxidative stress and inflammatory stress.

Objective:To develop a nomogram predictive model on the basis of identification of the risk factors associated with failure in repositioning the dislocation of the subaxial cervical spine with locked facets by skull traction.Methods:A retrospective study was conducted of the clinical data of the patients who had been treated for dislocation of the subaxial cervical spine with locked facets at Department of Orthopaedic Trauma, The Hospital Affiliated to Guizhou Medical University and Department of Spine Surgery, The People's Hospital of Guizhou Province from January 2014 to December 2022. The clinical data from The Hospital Affiliated to Guizhou Medical University were used as a training set (156 cases) and those from The People's Hospital of Guizhou Province as an external validation set (54 cases). Univariate analysis and multi-variate logistic regression analysis of the training set were conducted to screen out independent risk factors associated with the failure in repositioning the dislocation of the subaxial cervical spine with locked facets by skull traction. A nomogram predictive model was thus constructed and assessed by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Internal validation of the training set and external validation set was used to evaluate and validate the model.Results:The multivariate logistic regression analysis revealed that cervical Ⅰ grade dislocation ( P=0.002), cervical Ⅱ grade dislocation ( P=0.007), low segment affected ( P=0.042), unilateral facet locked ( P=0.027), and the ASIA grading of spinal cord injury ( P=0.008) were the independent risk factors associated with the failure in repositioning the dislocation of the subaxial cervical spine with locked facets by skull traction, based on which the nomogram model with a C-index of 0.88 was constructed to predict the failure in repositioning the dislocation of the subaxial cervical spine with locked facets by skull traction. Analysis of the ROC curve of the training set showed an area under the curve (AUC) of 0.88, indicating good accuracy of the nomogram model. Analysis of the calibration curve showed high consistency between the probability of the nomogram model predicting the failure in repositioning the dislocation of the subaxial cervical spine with locked facets by skull traction and the actual probability of traction reposition failure. Analysis of the decision curve showed that application of the nomogram model led to good benefits when the net benefit threshold for the failure in repositioning the dislocation of the subaxial cervical spine with locked facets by skull traction was 0.03 to 0.84. Analysis of the ROC curve of external validation set showed an AUC of 0.79, indicating good accuracy of the nomogram model. The training set showed a C-index of 0.87 after 1,000 internal verifications by the Bootstrap method, indicating good discrimination of the nomogram model. Conclusions:Cervical Ⅰ grade dislocation, cervical Ⅱ grade dislocation, low segment affected, unilateral facet locked, and incomplete spinal cord injury are independent risk factors associated with failure in repositioning the dislocation of the subaxial cervical spine with locked facets by skull traction. A nomogram model has been successfully constructed which can predict the failure in repositioning the dislocation of the subaxial cervical spine with locked facets by skull traction. Validation and evaluation of the nomogram model have demonstrated its good predictive value.

Objective:To investigate the influence of the depth of invasion on the prognosis of pT1 stage mid-thoracic esophageal cancer patients undergoing left thoracotomy.Methods:Retrospectively analyze the clinicopathological data of 139 patients with pT1N0M0 stage of mid-thoracic esophageal cancer who meet the enrollment criteria. Firstly, the prognosis and influencing factors of the whole group were analyzed. The differences in prognosis, local recurrence and distant metastasis between PT1A and PT1B patients were compared, and the influence of different infiltration depth on prognosis and treatment failure of patients was analyzed. SPSS 19.0 statistical software was used for statistical analysis.Results:The 1-year, 3-year and 5-year overall survival(OS) and disease-free survival(DFS) were 95.0%, 87.8%, 82.0% and 91.4%, 84.2%, 77.0%, respectively. There were significant differences in OS( χ2=7.500, P=0.006) and DFS( χ2=7.354, P=0.007) at 1, 3 and 5 years between pT1a and pT1b patients. Cox multivariate analysis showed that pT stage and pathological type were independent prognostic factors for OS and DFS( P<0.05). There were no significant differences in OS( χ2=0.734, P=0.693) and DFS( χ2=0.7690, P=0.681) of pT1a tumors with different invasion depths. There were significant differences in OS( χ2=15.368, P<0.001) and DFS( χ2=27.470, P<0.001) at 1, 3 and 5 years of pT1b tumors with different invasion depths. The recurrence rate of pT1b(23.8%) was significantly higher than that of pT1a(5.3%)( χ2=5.274, P=0.022). The distant metastasis rate of the former(10.9%) was also significantly higher than that of the latter(0)( χ2=4.494, P=0.034). There were significant differences in local recurrence rate( χ2=17.051, P<0.001) and distant metastasis rate( χ2=15.460, P<0.001) among pT1b patients with different infiltration depths. Logistic multivariate analysis showed that the depth of infiltration was an independent factor affecting the occurrence of local recurrence in stage pT1b patients after treatment( P<0.001). Pathological type( P=0.003) and infiltration depth( P=0.027) were independent factors affecting the occurrence of distant metastasis. Conclusion:pT1a period and pT1b period after the prognosis and treatment of patients with different failure modes, and pT1b period in patients with different infiltration depth and the prognosis of patients and its failure mode after treatment significantly related, infiltration depth of pT1b period after treatment in patients with the independence of the influencing factors of failure, suggest that clinical doctors should pay attention to pT1b period in patients with postoperative adjuvant therapy. This conclusion needs to be confirmed by large prospective studies of cases.

Protein aggregation is a critical issue in the production of biopharmaceuticals. During protein production, transport and storage, various factors can lead to protein aggregation. With the in-depth study, different ways of protein aggregation and various influencing factors were identified. This includes physical and chemical factors, translation modifications and protein structure. Since protein aggregation exerts major impact on the activity and homogeneity of proteins, it is of great importance to study the ways of protein aggregation and how to control it to obtain high-quality proteins. The review focuses on three ways of protein aggregation, namely 3D domain swapping, salt bridge formation, and oxidative stress, as well as methods to control protein aggregation during protein production, transport and storage. This may facilitate reducing the loss caused by the formation of protein aggregation and improving the purity and homogeneity of protein in research and commercial production.
Protein Aggregates ; Proteins/chemistry* ; Oxidative Stress

Objective:To investigate the clinical application of Grunenwald incision in cervicothoracic junction surgery.Methods:The clinical data of 25 patients with cervicothoracic junction tumor and 1 patient with cervicothoracic junction trauma in the single treatment group of Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from December 2011 to September 2021 were analyzed retrospectively, including 19 males and 7 females, aged 9-73 years old. Among the 26 patients, there were 9 cases of upper mediastinal tumor, 6 cases of superior sulcus tumor, 4 cases of thyroid tumor invading the upper mediastinal, 4 cases of chest wall tumor, 2 cases of esophageal cancer combined with supraclavicular lymph node metastasis, and 1 case of foreign body penetrating injury at the cervicothoracic junction. Grunenwald incision or additional posterolateral thoracic incision, median sternal incision, neck collar incision were used in all patients. The degree of tumor resection was evaluated. The operation time, intraoperative blood loss, length of hospital stay were observed, and the postoperative follow-up was analyzed.Results:There was no perioperative death in the whole group. 14 cases were treated with Grunenwald incision alone, 6 cases with additional posterolateral chest incision, 4 cases with additional neck collar incision, and 2 cases with additional median sternal incision. The tumors were completely resection in 22 cases, palliative tumor resection in 3 cases, and complete foreign body removal in 1 case. Postoperative pathology included 4 cases of schwannoma; 3 cases of lung adenocarcinoma, thyroid cancer and myofibroblastoma, respectively; 2 cases of supraclavicular lymph node metastasis of esophageal cancer and lung squamous carcinoma, respectively; 1 case of large cell neuroendocrine carcinoma, metastatic carcinoma of the first rib after lung squamous cell carcinoma, ganglioneuroma, nodular goiter, hemangioma, well differentiated liposarcoma, vascular endothelial tumor and cavernous angioma, respectively. The operation time was 120-430 min, with a mean of(226.92±88.40)min. The intraoperative blood loss was 100-1 000 ml, with a mean of(273.46±196.34)ml. The length of hospital stay was 6-26 days, with a mean of(12.73±4.46 )days. 26 patients were followed up for 6-130 months, with a mean of(57.88±43.64) months. During the follow-up period, 6 patients died.Conclusion:Grunenwald incision can provide good exposure of the structures near the cervicothoracic junction, preserve the integrity of sternoclavicular joint, reduce shoulder deformity, and has advantages for patients with cervicothoracic junction tumors, high rib resection, and cervicothoracic junction trauma.

Objective:To investigate the therapeutic efficiency of multiple forms of microdissected perforator flaps in the reconstruction of limb defect.Methods:The data of patients treated in the Department of Hand Surgery of Xuzhou Renci Hospital from June 2020 to June 2022 for repairing wound of hands, feet, limbs and popliteal fosses with microdissected perforator flap were retrospectively analyzed. CT angiography and color Doppler ultrasound were performed in all patients before surgery to locate perforator vessels, design the donor flap, and cut the flap retrograde according to the design line. After confirming good blood supple, the flap was harvested under the microscope, and fat particles were cut around the vascular pedicle by "insect eating" technique. After that, the flap was transferred to the recipient area, completed the vascular anastomosis, and placed the drainage tube. The donor site was closed directly. The blood circulation of the flap was observed closely after operation. Regular follow-up visits were conducted in outpatient clinics, door-to-door visits and WeChat to record sensory recovery and complications. Postoperative wound healing, flap shape, flap sensation, flap temperature and scar in donor area were evaluated using the efficacy satisfaction scale, which was divided into four grades: excellent (2 points), good (1 point), fair (0 point) and poor (-1 point). The total score of 5-10 was satisfactory, 0-4 was average, and -1--5 was unsatisfactory.Results:A total of 16 patients were included, including 8 males and 8 females. The age ranged from 26 to 65 years, with an average age of 45.9 years. There were 2 cases of upper limb soft tissue defect, 2 cases of hand degloving injury, 11 cases of hand skin soft tissue defect, and 1 case of popliteal soft tissue defect. The wound size ranged from 3.0 cm×4.5 cm to 13.0 cm×30.0 cm. Free medial sural artery perforator flap was used in 4 cases, interosseous dorsal artery perforator flap in 1 case, anterolateral femoral perforator flap in 6 cases, thoracic umbilical flap in 1 case, anterolateral femoral perforator flap combined with superficial circumflex iliac artery perforator flap in 1 case, and superficial circumflex iliac artery perforator flap in 3 cases. The size of the skin flap was 3.5 cm×5.0 cm - 9.5 cm×30.0 cm. After operation, 15 cases of flaps successfully survived, 1 case of venous crisis occurred 1 day after operation, and successfully survived after exploration and re-anastomosis of blood vessels. The wounds in the donor area healed in one stage without wound infection, delayed healing and other complications. All patients were follow-up for 7 to 18 months (mean 12.1 months), the skin flap survived well, no pigmentation, bloated appearance, and no patients requested secondary thinning treatment. The skin flap sensation recovered light touch in 1 case, protective sense in 9 cases and deep touch only in 6 cases. No significant thickening of skin flap was observed in the later period of follow-up, and skin flap wear was observed in 1 patient. There were only linear scars left in the donor area, and there were no obvious abnormalities in appearance and function. Efficacy satisfaction evaluation showed that all patients were satisfied with the therapeutic effect, scoring 6-9 points, with an average of 7.8 points.Conclusion:Microdissected perforator flap technique provides a one-stage surgical solution for aesthetic and functional areas with high requirements, and satisfactory clinical efficiencies can be obtained.